Objective To investigate the application of optimal antimicrobial therapies to controlling the increase of multidrug-resistant organisms. Methods Hospital rational use of antimicrobial drugs by strengthening the basic application and characteristics of generally used antimicrobial agents, early use of sensitive drugs based on the patient’s condition and constitution were encouraged. From January 2010 to December 2012, multidrug-resistant organisms were analyzed from various types of specimens. Results From January 2010 to December 2012, the annual proportion of bacterial strains slightly turned down (71.1% vs.59.3%), multidrug resistent organisms (MDRO). MDRO decreased slightly (2.70% vs.2.35%), with no significant difference (P>0.05). Detection of MDRO was significantly reduced from 0.19% to 0.14% (P<0.05). From January 2010 to December 2012, the detection rate of Klebsiella pneumoniae, Acinetobacter baumannii, MRSA and Pseudomonas aeruginosa all reduced from 0.4‰ to 0.3‰, methicillin resistant Staphylococcus aureus(MRSA) from 0.4‰ to 0.3‰. The proportions of Acinetobacter baumannii and MRSA were reduced from 23.0% to 19.1%, and 23.7% to 20.4%, respectively. Conclusions Reasonable selection of antibiotics can control the increase of multidrug-resistant organisms.